Purpose We sought to reduce the risk of infectious complications and non-relapse mortality (NRM) associated with the use of antithymocyte globulin (ATG) without compromising control of acute graft-versus-host disease (GVHD) in patients undergoing reduced intensity conditioning (RIC) transplantation. Methods As part of an ongoing quality improvement effort, we lowered the dose of rabbit ATG from 7.5 mg/kg of ATG (R-ATG) (n=39) to 6.0 mg/kg of ATG (r-ATG) (n=33) in association with fludarabine and busulfan RIC transplantation and then monitored patients for adverse events, relapse, and survival. Results Of the 72 mostly high risk (82%) patients studied, 89% received unrelated donor allografts, 25% of which were HLA-mismatched. No differences in post-transplantation full donor-cell chimerism rates were observed between the two ATG-dose groups (p>0.05). When R-ATG vs. r-ATG patients were compared, we observed no significant difference in the cumulative incidence of grade II–IV acute GVHD (32% vs. 27%; p-=0.73) or grade III–IV acute GVHD (23% vs. 11%; p=0.28). However, the r-ATG group had significantly less CMV reactivation (64% vs. 30%; p=0.005) and bacterial infections (56% vs. 18%; p=0.001), a better 1-year cumulative incidence of NRM (18% vs. 3%; p=0.03) and a trend for better 1-year overall survival (64% vs. 84%; p=0.07) compared to R-ATG patients. Conclusions A seemingly modest reduction in the dose of rabbit ATG did not compromise control of acute GVHD or achievement of donor chimerism but led to a significant decrease in the risk of serious infections and NRM in high risk RIC allograft recipients.

The SARS-CoV-2 can lead to severe illness with COVID-19. Outcomes of patients requiring mechanical ventilation are poor. Awake proning in COVID-19 improves oxygenation, but on data clinical outcomes is limited. This single-centre retrospective study aimed to assess whether successful awake proning of patients with COVID-19, requiring respiratory support (continuous positive airways pressure (CPAP) or high-flow nasal oxygen (HFNO)) on a respiratory high-dependency unit (HDU), is associated with improved outcomes. HDU care included awake proning by respiratory physiotherapists. Of 565 patients admitted with COVID-19, 71 (12.6%) were managed on the respiratory HDU, with 48 of these (67.6%) requiring respiratory support. Patients managed with CPAP alone 22/48 (45.8%) were significantly less likely to die than patients who required transfer onto HFNO 26/48 (54.2%): CPAP mortality 36.4%; HFNO mortality 69.2%, (p=0.023); however, multivariate analysis demonstrated that increasing age and the inability to awake prone were the only independent predictors of COVID-19 mortality. The mortality of patients with COVID-19 requiring respiratory support is considerable. Data from our cohort managed on HDU show that CPAP and awake proning are possible in a selected population of COVID-19, and may be useful. Further prospective studies are required.

Summary:Long-term outcome was analyzed in 28 patients transplanted between 1989 and 1992 following busulfan and cyclophosphamide and who had busulfan levels studied. While there was no significant correlation of busulfan levels with diagnosis, patients who had received extensive prior chemotherapy had a significantly higher area under the curve (AUC; P = 0.02) and maximum busulfan levels (Cmax; P = 0.03). High AUC was associated with the development of hepatic veno-occlusive disease (P = 0.03) and with early transplant-related mortality (P = 0.06). No significant correlation of busulfan levels with relapse, late non-relapse death, late complications, nor event-free survival was detected. Bone Marrow Transplantation (2001) 27, 1121-1124.

Health Services and Delivery ResearchISSN 2050-4349 (Print) ISSN 2050-4357 (Online) This journal is a member of and subscribes to the principles of the Committee on Publication Ethics (COPE) (www.publicationethics.org/).Editorial contact: journals.library@nihr.ac.ukThe full HS&DR archive is freely available to view online at www.journalslibrary.nihr.ac.uk/hsdr. Print-on-demand copies can be purchased from the report pages of the NIHR Journals Library website: www.journalslibrary.nihr.ac.uk Criteria for inclusion in the Health Services and Delivery Research journalReports are published in Health Services and Delivery Research (HS&DR) if (1) they have resulted from work for the HS&DR programme or programmes which preceded the HS&DR programme, and (2) they are of a sufficiently high scientific quality as assessed by the reviewers and editors. HS&DR programmeThe Health Services and Delivery Research (HS&DR) programme, part of the National Institute for Health Research (NIHR), was established to fund a broad range of research. It combines the strengths and contributions of two previous NIHR research programmes: the Health Services Research (HSR) programme and the Service Delivery and Organisation (SDO) programme, which were merged in January 2012.The HS&DR programme aims to produce rigorous and relevant evidence on the quality, access and organisation of health services including costs and outcomes, as well as research on implementation. The programme will enhance the strategic focus on research that matters to the NHS and is keen to support ambitious evaluative research to improve health services.For more information about the HS&DR programme please visit the website: http://www.nets.nihr.ac.uk/programmes/hsdr This reportThe research reported in this issue of the journal was funded by the HS&DR programme or one of its preceding programmes as project number 12/209/51. The contractual start date was in May 2014. The final report began editorial review in August 2016 and was accepted for publication in April 2017. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HS&DR editors and production house have tried to ensure the accuracy of the authors' report and would like to thank the reviewers for their constructive comments on the final report document. However, they do not accept liability for damages or losses arising from material published in this report.This report presents independent research funded by the National Institute for Health Research (NIHR). The views and opinions expressed by authors in this publication are those of the authors and do not necessarily reflect those of the NHS, the NIHR, NETSCC, the HS&DR programme or the Department of Health and Social Care. If there are verbatim quotations included in this publication the views and opinions expressed by the interviewees are those of the interviewees and do not necessarily reflect those of the authors, those of the NHS, the NIHR, NETSCC, the HS&DR programme or the Departm...

Summary Complex karyotype (CK) on metaphase cytogenetics discriminates poor outcome in chronic lymphocytic leukaemia (CLL) patients undergoing salvage treatment; we hypothesized that it might provide prognostic information for patients undergoing allogeneic stem cell transplant. Fifty-one CLL patients were analysed following transplant; 18-month overall survival (OS), event-free survival (EFS) and cumulative incidence of progression estimates were 35%, 14% and 63%, respectively, in patients with CK (n = 19) versus 83%, 68% and 29% in patients without (n = 32) (P ≤ 0.0001, P ≤ 0.0001, and P = 0.02). In patients with high-risk interphase cytogenetics, CK remained predictive of worse OS (P = 0.02) and EFS (P = 0.009). These findings support further evaluation of metaphase karyotype in transplant risk assessment.

BackgroundDigital communication between a patient and their clinician offers the potential for improved patient care, particularly for young people with long term conditions who are at risk of service disengagement. However, its use raises a number of ethical questions which have not been explored in empirical studies. The objective of this study was to examine, from the patient and clinician perspective, the ethical implications of the use of digital clinical communication in the context of young people living with long-term conditions.MethodsA total of 129 semi-structured interviews, 59 with young people and 70 with healthcare professionals, from 20 United Kingdom (UK)-based specialist clinics were conducted as part of the LYNC study. Transcripts from five sites (cancer, liver, renal, cystic fibrosis and mental health) were read by a core team to identify explicit and implicit ethical issues and develop descriptive ethical codes. Our subsequent thematic analysis was developed iteratively with reference to professional and ethical norms.ResultsClinician participants saw digital clinical communication as potentially increasing patient empowerment and autonomy; improving trust between patient and healthcare professional; and reducing harm because of rapid access to clinical advice. However, they also described ethical challenges, including: difficulty with defining and maintaining boundaries of confidentiality; uncertainty regarding the level of consent required; and blurring of the limits of a clinician’s duty of care when unlimited access is possible. Paradoxically, the use of digital clinical communication can create dependence rather than promote autonomy in some patients. Patient participants varied in their understanding of, and concern about, confidentiality in the context of digital communication. An overarching theme emerging from the data was a shifting of the boundaries of the patient-clinician relationship and the professional duty of care in the context of use of clinical digital communication.ConclusionsThe ethical implications of clinical digital communication are complex and go beyond concerns about confidentiality and consent. Any development of this form of communication should consider its impact on the patient-clinician-relationship, and include appropriate safeguards to ensure that professional ethical obligations are adhered to.

Patients with chemorefractory aggressive non-Hodgkin’s lymphomas (NHL) generally have poor clinical outcomes with available therapies. Allogeneic transplantation may be curative, but few studies are available to guide transplant decision making in this setting. We examined allogeneic transplantation outcomes for 46 patients with chemorefractory, aggressive NHL patients who had either stable disease (SD, n=32) or progressive disease (PD, n=14), respectively, following last salvage treatment. The median age was 46 years (range 22–63 yrs). 39 patients received matched sibling allografts, while 7 underwent unrelated donor transplantation. Diagnoses included diffuse large B-cell lymphoma (n=18), Burkitt’s lymphoma (n=3), transformed B-cell lymphoma (n=5), mantle cell lymphoma (n=11) and peripheral T-cell lymphoma (n=9). The median number of prior therapies was 3 (range 2–8). Median follow-up of surviving patients is 5-years. 5-year overall survival (OS), progression free survival (PFS), and relapse rate for the whole cohort (n=46) were 38%, 34%, and 35% respectively. The rate of grade II–IV acute graft-versus-host disease (GVHD) was 43%. Of the 33 evaluable patients 75% developed chronic GVHD. Overall non-relapse mortality rate was 34%. The 5-year OS and PFS rates for patients with SD and PD were 46% vs. 21% (p-value=0.01; log-rank test), and 46% vs. 7% (p-value=0.0002; log-rank test) respectively. This study confirms that allogeneic transplant is curative for a subset of chemorefractory patients with SD. However, patients with PD had uniformly poor outcomes following allografting with conventional conditioning approaches. Given the outcomes seen here in the setting of PD, such patients should proceed with transplant only in the setting of investigational therapy.

Infliximab, a chimeric monoclonal antibody against tumor necrosis factor-α, has shown activity against steroid refractory acute graft-versus-host disease (GVHD). We conducted a prospective trial of infliximab for the prophylaxis of acute GVHD. Patients older than 20 years undergoing myeloablative allogeneic stem cell transplantation for hematologic malignancies were eligible. GVHD prophylaxis consisted of infliximab given one day prior to conditioning and then on days 0, +7, +14, +28 and +42, together with standard cyclosporine and methotrexate. Nineteen patients with a median age of 53 years were enrolled. All patients received peripheral blood allografts from matched sibling (n=14) or unrelated donors (n=5). Results were compared with a matched historical control group (n=30) treated contemporaneously at our institution. The cumulative incidences of grades II–IV acute GVHD in the infliximab and control groups were 36.8% and 36.6% respectively (p=0.77). Rates of chronic GVHD were 78% and 61% respectively (p=0.22). Significantly more bacterial and invasive fungal infections were observed in the infliximab group (p=0.01 and p=0.02 respectively). Kaplan-Meier estimates of 2 year overall survival and progression free survival for patients receiving infliximab were 42% and 36% respectively. The corresponding numbers for patients in the control group were 46% and 43% respectively. The addition of infliximab to standard GVHD prophylaxis did not lower the risk of GVHD and was associated with an increased risk of bacterial and invasive fungal infections.